Pertussis Toxin-sensitive G Proteins Regulate Lymphoid Lineage Specification in Multipotent Hematopoietic Progenitors

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2009 Apr 14

PMID 19363218

Citations 12

Authors

Anne Y Lai

Akiko Watanabe

Tommy OBrien

Motonari Kondo

Affiliations

Soon will be listed here.

Abstract

Lymphoid and myeloid lineage segregation is a major developmental step during early hematopoiesis from hematopoietic stem cells. It is not clear, however, whether multipotent progenitors (MPPs) adopt a lymphoid or myeloid fate through stochastic mechanisms, or whether this process can be regulated by extracellular stimuli. In this study, we show that lymphoid lineage specification occurs in MPPs before lymphoid lineage priming, during which MPPs migrate from the proximal to the distal region relative to the endosteum of the bone marrow. Lymphoid-specified MPPs have low myeloid differentiation potential in vivo, but potently differentiate into myeloid cells in vitro. When treated with pertussis toxin, an inhibitor of G protein-coupled receptor signaling, lymphoid-specified MPPs regain in vivo myeloid potential, and their localization is dispersed in the bone marrow. These results clearly demonstrate that specific microenvironments that favorably support lymphoid or myeloid lineage development exist at structurally distinct regions in the bone marrow.

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References

Jeremiah Bell J, Bhandoola A . The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature. 2008; 452(7188):764-7. DOI: 10.1038/nature06840. View

Hu M, Krause D, Greaves M, Sharkis S, Dexter M, Heyworth C . Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev. 1997; 11(6):774-85. DOI: 10.1101/gad.11.6.774. View

Kiel M, Yilmaz O, Iwashita T, Yilmaz O, Terhorst C, Morrison S . SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-21. DOI: 10.1016/j.cell.2005.05.026. View

Goldsmith M, Mikami A, You Y, Liu K, Thomas L, Pharr P . Absence of cytokine receptor-dependent specificity in red blood cell differentiation in vivo. Proc Natl Acad Sci U S A. 1998; 95(12):7006-11. PMC: 22719. DOI: 10.1073/pnas.95.12.7006. View

Wineman J, Moore K, Lemischka I . Functional heterogeneity of the hematopoietic microenvironment: rare stromal elements maintain long-term repopulating stem cells. Blood. 1996; 87(10):4082-90. View

Nilsson S, Johnston H, Coverdale J . Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood. 2001; 97(8):2293-9. DOI: 10.1182/blood.v97.8.2293. View

Lai A, Lin S, Kondo M . Heterogeneity of Flt3-expressing multipotent progenitors in mouse bone marrow. J Immunol. 2005; 175(8):5016-23. DOI: 10.4049/jimmunol.175.8.5016. View

Igarashi H, Gregory S, Yokota T, Sakaguchi N, Kincade P . Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity. 2002; 17(2):117-30. DOI: 10.1016/s1074-7613(02)00366-7. View

Xie Y, Yin T, Wiegraebe W, He X, Miller D, Stark D . Detection of functional haematopoietic stem cell niche using real-time imaging. Nature. 2008; 457(7225):97-101. DOI: 10.1038/nature07639. View

10.

Terskikh A, Miyamoto T, Chang C, Diatchenko L, Weissman I . Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood. 2003; 102(1):94-101. DOI: 10.1182/blood-2002-08-2509. View

11.

Kehrl J . Heterotrimeric G protein signaling: roles in immune function and fine-tuning by RGS proteins. Immunity. 1998; 8(1):1-10. DOI: 10.1016/s1074-7613(00)80453-7. View

12.

Suda T, Arai F, Hirao A . Hematopoietic stem cells and their niche. Trends Immunol. 2005; 26(8):426-33. DOI: 10.1016/j.it.2005.06.006. View

13.

Murre C . Defining the pathways of early adult hematopoiesis. Cell Stem Cell. 2008; 1(4):357-8. DOI: 10.1016/j.stem.2007.09.008. View

14.

Semerad C, Poursine-Laurent J, Liu F, Link D . A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation. Immunity. 1999; 11(2):153-61. DOI: 10.1016/s1074-7613(00)80090-4. View

15.

Kuwata N, Igarashi H, Ohmura T, Aizawa S, Sakaguchi N . Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene. J Immunol. 1999; 163(12):6355-9. View

16.

Nagasawa T . Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol. 2006; 6(2):107-16. DOI: 10.1038/nri1780. View

17.

Nie Y, Han Y, Zou Y . CXCR4 is required for the quiescence of primitive hematopoietic cells. J Exp Med. 2008; 205(4):777-83. PMC: 2292218. DOI: 10.1084/jem.20072513. View

18.

Hsu C, Kikuchi K, Kondo M . Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment. Blood. 2007; 110(5):1420-8. PMC: 1975832. DOI: 10.1182/blood-2007-02-071761. View

19.

Stoffel R, Ziegler S, Ghilardi N, Ledermann B, de Sauvage F, Skoda R . Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo. Proc Natl Acad Sci U S A. 1999; 96(2):698-702. PMC: 15199. DOI: 10.1073/pnas.96.2.698. View

20.

Miyamoto T, Iwasaki H, Reizis B, Ye M, Graf T, Weissman I . Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell. 2002; 3(1):137-47. DOI: 10.1016/s1534-5807(02)00201-0. View